Large-scale plasma-metabolome analysis identifies potential biomarkers of psoriasis and its clinical subtypes
Toshihiro Kishikawa, Noriko Arase, Shigeyoshi Tsuji, Yuichi Maeda, Takuro Nii, Jun Hirata, Ken Suzuki, Kenichi Yamamoto, Tatsuo Masuda, Kotaro Ogawa, Shiro Ohshima, Hidenori Inohara, Atsushi Kumanogoh, Manabu Fujimoto, Yukinori Okada
Abstract
BackgroundPsoriasis is an immune-mediated skin disease for which the crosstalk between genetic and environmental factors is responsible. To date, no definitive diagnostic criteria for psoriasis yet, and specific biomarkers are required.ObjectiveWe performed metabolome analysis to identify metabolite biomarkers of psoriasis and its subtypes such as psoriatic arthritis (PsA) and cutaneous psoriasis (PsC).MethodsWe constructed metabolomics profiling of 130 plasma samples (42 PsA patients, 50 PsC patients, and 38 healthy controls) using a nontargeted metabolomics approach.ResultsPsoriasis-control association tests showed that one metabolite (ethanolamine phosphate) was significantly increased in psoriasis samples than in the controls, whereas three metabolites decreased (false discovery rate [FDR] < 0.05; XA0019, nicotinic acid, and 20α-hydroxyprogesterone). In the association test between PsA and PsC, tyramine significantly increased in PsA than in PsC, whereas mucic acid decreased (FDR < 0.05). Molecular pathway analysis of the PsA–PsC association test identified enrichment of vitamin digestion and absorption pathway in PsC (P = 1.3 × 10−4). Correlation network analyses elucidated that a subnetwork centered on aspartate was constructed among the psoriasis-associated metabolites; meanwhile, the major subnetwork among metabolites with differences between PsA and PsC was primarily formed from saturated fatty acids.ConclusionOur large-scale metabolome analysis highlights novel characteristics of plasma metabolites in psoriasis and the differences between PsA and PsC, which could be used as potential biomarkers of psoriasis and its clinical subtypes. These findings contribute to our understanding of psoriasis pathophysiology.